| 1. |
- Bengtsson, Magnus W., et al.
(författare)
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Food-induced expression of orexin receptors in rat duodenal mucosa regulates the bicarbonate secretory response to orexin-A
- 2007
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Ingår i: American Journal of Physiology - Gastrointestinal and Liver Physiology. - : American Physiological Society. - 0193-1857 .- 1522-1547. ; 293:2, s. G501-G509
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Tidskriftsartikel (refereegranskat)abstract
- Presence of appetite-regulating peptides orexin-A and orexin-B in mucosal endocrine cells suggests a role in physiological control of the intestine. Our aim was to characterize orexin-induced stimulation of duodenal bicarbonate secretion and modulation of secretory responses and mucosal orexin receptors by overnight food deprivation. Lewis x Dark Agouti rats were anesthetized and proximal duodenum cannulated in situ. Mucosal bicarbonate secretion (pH stat) and mean arterial blood pressure were continuously recorded. Orexin-A was administered intra-arterially close to the duodenum, intraluminally, or into the brain ventricles. Total RNA was extracted from mucosal specimens, reverse transcribed to cDNA and expression of orexin receptors 1 and 2 (OX1 and OX2) measured by quantitative real-time PCR. OX1 protein was measured by Western blot. Intra-arterial orexin-A (60–600 nmol·h–1·kg–1) increased (P < 0.01) the duodenal secretion in fed but not in fasted animals. The OX1 receptor antagonist SB-334867, which was also found to have a partial agonist action, abolished the orexin-induced secretory response but did not affect secretion induced by the muscarinic agonist bethanechol. Atropine, in contrast, inhibited bethanechol but not orexin-induced secretion. Orexin-A infused into the brain ventricles (2–20 nmol·kg–1·h–1) or added to luminal perfusate (1.0–100 nM) did not affect secretion, indicating that orexin-A acts peripherally and at basolateral receptors. Overnight fasting decreased mucosal OX1 and OX2 mRNA expression (P < 0.01) as well as OX1 protein expression (P < 0.05). We conclude that stimulation of secretion by orexin-A may involve both receptor types and is independent of cholinergic pathways. Intestinal OX receptors and secretory responses are markedly related to food intake.
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| 2. |
- Bengtsson, Magnus W., et al.
(författare)
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Short food deprivation inhibits orexin receptor 1 expression and orexin-A induced intracellular calcium signaling in acutely isolated duodenal enterocytes
- 2009
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Ingår i: American Journal of Physiology - Gastrointestinal and Liver Physiology. - : American Physiological Society. - 0193-1857 .- 1522-1547. ; 296:3, s. G651-G658
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Tidskriftsartikel (refereegranskat)abstract
- Bengtsson MW, Makela K, Herzig KH, Flemstrom G. Short food deprivation inhibits orexin receptor 1 expression and orexin-A induced intracellular calcium signaling in acutely isolated duodenal enterocytes. Am J Physiol Gastrointest Liver Physiol 296: G651-G658, 2009. First published December 31, 2008; doi:10.1152/ajpgi.90387.2008.-Close intra-arterial infusion of the appetite regulating peptide orexin-A stimulates bicarbonate secretion from the duodenal mucosa. The aim of the present study was to elucidate the ability of orexin-A to induce intracellular calcium signaling in acutely isolated duodenal enterocytes. Freshly isolated clusters of enterocytes, obtained from rat duodenal mucosa or human duodenal biopsies, were loaded with fura 2-AM and mounted in a perfusion chamber. Cryptlike enterocytes were selected (caged), and changes in intracellular calcium concentration ([Ca2+](i)) were evaluated by fluorescence imaging. Total RNA was extracted from pellets of enterocytes and reverse transcribed to cDNA, and expression of orexin receptors 1 and 2 (OX1R and OX2R) was measured by quantitative real-time PCR. Orexin-A at all concentrations tested (1-100 nM) increased [Ca2+](i) in enterocytes isolated from continuously fed rats, and the OX1R-antagonist SB-334867 (10 nM) attenuated the response. The primary [Ca2+](i) response was a slow increase to a sustained plateau persisting after orexin-A removal, and a similar response was observed in enterocytes from human biopsies. In contrast to orexin-A, the OX2R agonist (Ala(11), D-Leu(15))orexin-B (1-10 nM) did not induce calcium signaling. There were no significant [Ca2+](i) responses in enterocytes from animals food deprived overnight, and overnight fasting decreased (P < 0.01) enterocyte OX1R as well as OX2R mRNA. Induction of intracellular calcium signaling in isolated duodenal enterocytes is thus mediated primarily by OX1R receptors. Short (overnight) food deprivation markedly depresses receptor expression and inhibits orexin-A induced increases in [Ca2+](i). Studies of enterocyte signaling and intestinal secretion requires particular evaluation regarding feeding status.
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| 3. |
- Pilvi, Taru-K., et al.
(författare)
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Metabolomic changes in fatty liver can be modified by dietary protein and calcium during energy restriction
- 2008
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Ingår i: World Journal of Gastroenterology. - : Baishideng Publishing Group Co., Limited. - 1007-9327 .- 2219-2840. ; 14:28, s. 4462-4472
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To characterise the effect of energy restriction (ER) on liver lipid and primary metabolite profile by using metabolomic approach. We also investigated whether the effect of energy restriction can be further enhanced by modification of dietary protein source and calcium.METHODS: Liver metabolomic profile of lean and obese C57Bl/6J mice (n = 10/group) were compared with two groups of weight-reduced mice. ER was performed on control diet and whey protein-based high-calcium diet (whey + Ca). The metabolomic analyses were performed using the UPLC/MS based lipidomic platform and the HPLC/MS/MS based primary metabolite platform.RESULTS: ER on both diets significantly reduced hepatic lipid accumulation and lipid droplet size, while only whey + Ca diet significantly decreased blood glucose (P < 0.001) and serum insulin (P < 0.01). In hepatic lipid species the biggest reduction was in the level of triacylglycerols and ceramides while the level of cholesterol esters was significantly increased during ER. Interestingly, diacylglycerol to phospholipid ratio, an indicator of relative amount of diabetogenic diglyceride species, was increased in the control ER group, but decreased in the whey + Ca ER group (P < 0.001, vs obese). ER on whey + Ca diet also totally reversed the obesity induced increase in the relative level of lipotoxic ceramides (P < 0.001, vs obese; P > 0.05, vs lean). These changes were accompanied with up-regulated TCA cycle and pentose phosphate pathway metabolites.CONCLUSION: ER-induced changes on hepatic metabolomic profile can be significantly affected by dietary protein source. The therapeutic potential of whey protein and calcium should be further studied.
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